Interesting case and approach

[deleted4401]

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I had an interesting case yesterday, and curious to see others would have approached.

70 yo woman with controlled DM, HTN who had been getting annual mammograms noted a palpable mass in her R breast. Went to gyn, no palpable axillary LAD. Was referred for dx mammogram and US. Significant change from prior mammogram, large 6-7 cm abnormality seen, and also seen on US. Referred for image guided bx and was found to have ILC, ER+, PR+, Her 2 Neu -. Surgeon saw her and recommended mastectomy/sentinel lymph node bx. Path showed 6cm tumor, negative margins (closest 0.5cm), no LVSI, no skin/muscle/nipple involvement. One sentinel lymph node was hot/blue and was negative on frozen/H&E, but b/c lobular histology, the local academic center auto-runs IHC on it. It came IHC+. PET/CT for staging negative. So, pT3N0(i+)M0.

They discussed the case at their tumor board, and came to the conclusion that skip ALND, treat chest wall and full axilla with RT.

Saw med-onc. They didn't run an OncoType - would you guys have wanted one? Going to get TC x 6

Saw me. My thoughts - in pre-IHC era, this lady was pT3N0, no adverse factors, clean margins, and I would have assessed her risk of LR at 7-8% (NSABP, MDACC/MGH series) and offered her the choice of chest wall RT vs no RT, with no strong leaning on my side. But, knowing she is IHC positive confuses things.

I ran her through the MSKCC nomogram, and her risk for having further disease in axilla was 29%. Put her through the other nomogram for having 4 or more nodes positive, and that was about 5-7%. I talked to the surgeon again, and she wasn't excited about an ALND.

In my head, she has a low risk of chest wall recurrence, regardless of the IHC status, but I don't know any data to suggest that is true (except knowing that the large series of T3N0 didn't have IHC status and they still had a good outcome), but I think 29% risk of axillary disease is high enough to warrant treatment. I'd prefer a dissection, but I don't feel strongly about it. I don't think it's okay to treat the axilla without treating the chest wall (because I've never seen that), so I'm going to do high tangents, and supplement if necessary with another field. As far as apex/SCV, again, since she has a low risk of disease, I'd rather not treat, but it is low toxicity and I'm in the neighborhood.

What bums me out is that if I didn't have IHC status, I would have leaned against treating at all. Now, b/c of IHC, I'm treating EVERYTHING.

How would the rest of you have thought this case through?

-S

 

[Gfunk6]

We actually had two very similar cases on our breast service recently. To address some of your issues:

1. Oncotoype: in this patient's case I think it would not be helpful. I don't think any reasonable Med Onc would consider forgoing chemo simply b/c the score was low or intermediate.

2. Completion ALND: In concur that this should be skipped. There is an increasing body of literature showing that a + SLNB alone is probably equivalent to ALND in most women. There is a good series from MSKCC (PMID: 15319717). The fact that she is older, lacks LVI, is luminal A subtype, has no macromets and has no ECE all bode well for her prognosis. Her risk of axillarly LN failure is probably < 5% (comprable with MSKCC nomogram).

3. CW RT: This issue is a bit more controversial. If you look at the ACR PMRT criteria paper (PMID: 19251087) there is a good summary of what factors might sway you to hit the green button on RT in borderline cases. In your patient, I think the only bit of info you haven't given us is grade. If she were grade 1/2 I would be comfortable forgoing RT. However grade 3 would probably sway me.

 

[Palex80]

You may wanna also like to have a look at this paper:
http://www.ncbi.nlm.nih.gov/pubmed/18996609

I would say that her LR risk is probably slightly less than 10% and that's reason enough for me to treat her IHC positive or not.


I am not sure I would treat the axilla, I'd probably like to treat the area around the involved node within the tangents. I would not treat the SCV unless the tumor was initially located in the upper quadrants.

 

[qwert]

Tough case.

1) Agree - no role for Oncotype whatsoever.

2) What was the Nottingham grade? If poorly differentiated, that would tilt you further towards treating CW and perhaps axilla.

I had an interesting case yesterday, and curious to see others would have approached.

70 yo woman with controlled DM, HTN who had been getting annual mammograms noted a palpable mass in her R breast. Went to gyn, no palpable axillary LAD. Was referred for dx mammogram and US. Significant change from prior mammogram, large 6-7 cm abnormality seen, and also seen on US. Referred for image guided bx and was found to have ILC, ER+, PR+, Her 2 Neu -. Surgeon saw her and recommended mastectomy/sentinel lymph node bx. Path showed 6cm tumor, negative margins (closest 0.5cm), no LVSI, no skin/muscle/nipple involvement. One sentinel lymph node was hot/blue and was negative on frozen/H&E, but b/c lobular histology, the local academic center auto-runs IHC on it. It came IHC+. PET/CT for staging negative. So, pT3N0(i+)M0.

They discussed the case at their tumor board, and came to the conclusion that skip ALND, treat chest wall and full axilla with RT.

Saw med-onc. They didn't run an OncoType - would you guys have wanted one? Going to get TC x 6

Saw me. My thoughts - in pre-IHC era, this lady was pT3N0, no adverse factors, clean margins, and I would have assessed her risk of LR at 7-8% (NSABP, MDACC/MGH series) and offered her the choice of chest wall RT vs no RT, with no strong leaning on my side. But, knowing she is IHC positive confuses things.

I ran her through the MSKCC nomogram, and her risk for having further disease in axilla was 29%. Put her through the other nomogram for having 4 or more nodes positive, and that was about 5-7%. I talked to the surgeon again, and she wasn't excited about an ALND.

In my head, she has a low risk of chest wall recurrence, regardless of the IHC status, but I don't know any data to suggest that is true (except knowing that the large series of T3N0 didn't have IHC status and they still had a good outcome), but I think 29% risk of axillary disease is high enough to warrant treatment. I'd prefer a dissection, but I don't feel strongly about it. I don't think it's okay to treat the axilla without treating the chest wall (because I've never seen that), so I'm going to do high tangents, and supplement if necessary with another field. As far as apex/SCV, again, since she has a low risk of disease, I'd rather not treat, but it is low toxicity and I'm in the neighborhood.

What bums me out is that if I didn't have IHC status, I would have leaned against treating at all. Now, b/c of IHC, I'm treating EVERYTHING.

How would the rest of you have thought this case through?

-S

 

[deleted4401]

Grade 1.

 

[Palex80]

I ran the patient's case in adjuvant online: It came up with a 3.5% absolute benefit through 3rd generation chemotherapy in comparison to hormonal therapy only. I classified this patient as nodal negative in the tool.

3,5% additional overall survival benefit with the chemo. That's not much.


Now, lets look at the matter from the Overgaards' point of view:
http://www.ncbi.nlm.nih.gov/pubmed/18471914

According to the Overgaards this patient would fit into the intermediate prognosis group, due to the large size of the primary tumor.
In the Overgaards publication the ratio of overall survival benefit to recurrence free survival benefit in these patients is 1:2, meaning that in order to "save" one patient from death you need to avoid two local recurrencies.

Let's say that our patient has a LR risk of 9% without radiation therapy and we lower this to 3% with treatment.
That would mean a 6% absolute gain in LR-freedom, resulting into a 3% absolute overall survival benefit though radiation therapy, when applying the Overgaards' rule.

That's practically what chemotherapy managed too.

Hmmm...

What would you rather have if you were 70?
6x TC or 50 Gy chest wall + lymphatics irradiation?

If the med. oncs decided to give these poor lady 6x TC for 3,5% OS gain, I see no reason why you should omit radiation therapy.

 

[temujim]

Combined analysis of danish/eortc (PMID: 11250998) suggested that lobular histology itself is a risk factor. Post mastectomy without radiation had a 18% local recurrence rate at 10 yrs. And those patients were lower risk stage I-II (randomized to BCT vs Mast).

Not aware of any data specifically for local control and IHC+, but large retrospective stuff (including recent NEJM) indicates worsened DFS.

I think it is reasonable to do a hypofractionated course (given her age); perhaps omit the scar boost as recently discussed.

 

[medgator]

2. Completion ALND: In concur that this should be skipped. There is an increasing body of literature showing that a + SLNB alone is probably equivalent to ALND in most women. There is a good series from MSKCC (PMID: 15319717). The fact that she is older, lacks LVI, is luminal A subtype, has no macromets and has no ECE all bode well for her prognosis. Her risk of axillarly LN failure is probably < 5% (comprable with MSKCC nomogram).

Monica Morrow gave a nice talk reviewing this information at our hospital recently. It certainly is compelling to think about, although one has to wonder how do we incorporate this information into our existing body of literature (i.e. potential OS benefit for PMRT in node-positive pts in a combined analysis of the Danish 82 studies).

Another big caveat that came up during her discussion of that study was that a large portion of those pts ended up getting standard whole-breast XRT, which probably ended up sterilizing any potential residual disease in the axilla.

From the paper:

A second caveat is whether our observed low rate of axillary LR in the era of SLN biopsy is simply the result of contemporary adjuvant treatments; chemotherapy, tamoxifen, and RT all act to reduce LR independently of surgery. In our own internal audit, more than half of the SLN-positive/no ALND cohort patients who were treated at MSKCC received RT, which was modified to better treat the axilla.

So that's something else to consider if this lady won't get getting a full ALND. It's also important to consider this if you were looking to use partial breast techniques for a pt in this situation if she had received a lumpectomy instead of an MRM.

 

[deleted4401]

I think I've been swayed into skipping treating the axilla, at least trying to give it a full dose. Whatever is caught in the tangents is fine.

People really gotta study IHC+ disease more. It's really F'ing up trying to analyze the data... Seriously wish I didn't have that information, b/c I still don't know what to do with it.

I'm surprised that nobody wants the OncoType. T predicts N predicts outcome, but if T high and N is negative, that's alternative biology and it would be nice to know recurrence scores for this group of patients and outcomes

-S

 

[qwert]

Simul,
OncoType was developed on NSABP B-14 pts, majority of whom were T1 (<5% larger than 4cm). Thus OncoType may not be used for evaluating locally advanced cancers.

Your former institution had a financial stake in OncoType, and therefore it's heavily over-utilized in that part of the country. NCCN guidelines give a fairly good idea of when OncoType is actually indicated and is safe to use.

I think I've been swayed into skipping treating the axilla, at least trying to give it a full dose. Whatever is caught in the tangents is fine.

People really gotta study IHC+ disease more. It's really F'ing up trying to analyze the data... Seriously wish I didn't have that information, b/c I still don't know what to do with it.

I'm surprised that nobody wants the OncoType. T predicts N predicts outcome, but if T high and N is negative, that's alternative biology and it would be nice to know recurrence scores for this group of patients and outcomes

-S

 

[deleted4401]

If I limited my use of clinical technology to those that my former institution did not have a financial stake in, I would be treating with Cobalt and Radium needles 🙂

I know what OncoType was validated on. I just think it's arbitrary to say that a genetic test is useful for a tumor that is 3.9cm, but not one that is 5.1 cm. There is now data on node positive patients, as well, and those patients were not in the original data set.

-S

 

[Palex80]

People really gotta study IHC+ disease more. It's really F'ing up trying to analyze the data... Seriously wish I didn't have that information, b/c I still don't know what to do with it.

There are some more data coming from the Duth MIRROR study on risk of isolated axillary recurrence in the case of incomplete dissection with positive sentinel nodes.:
http://meeting.ascopubs.org/cgi/content/abstract/27/18S/CRA506

According to these data, the risk is quite low without axillary treatment, roughly 2%, in the case of only IHC+.
However you do have to take in mind, that your patient has quite a large primary.